Cooperative Motor Control Of The Pyloric Junction By Myogenic And Neuronal Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$271,527.00
Summary
The coordinated muscle movement in the junction between the stomach and small intestine is an essential mechanism for controlling the speed of gastric content moving into the intestine for further digestion. The muscle movement determines the gastric emptying at an optimal rate and prevents intestinal contents reflux to the stomach. Failure of this coordination is likely to be involved in a variety of clinical conditions including accelerated or delayed gastric emptying. Up to date, little infor ....The coordinated muscle movement in the junction between the stomach and small intestine is an essential mechanism for controlling the speed of gastric content moving into the intestine for further digestion. The muscle movement determines the gastric emptying at an optimal rate and prevents intestinal contents reflux to the stomach. Failure of this coordination is likely to be involved in a variety of clinical conditions including accelerated or delayed gastric emptying. Up to date, little information is available about the interaction between nerve, muscle and pacemaker cells during this coordinated movement. In this project, we will investigate how the nerve, muscle and pacemaker cells work together to control this coordinated movement. We will study this mechanism at both cellular and organ levels and try to establish the patterns of muscle movement and their coordination between the stomach and the small intestine. The interaction between the nerve and pacemaker cells will be characterised in these studies. Our work will provide structural evidence for this activity. It includes identification of the nerve pathways connecting between the small intestine and stomach and determination of whether the pacemaker cell network is an uniform continuous or a discontinuous or a transitional structure across the junction. These studies will reveal the correlation between pacemaker cell mediated activity and the density of these cells in each junctional region. We will also determine whether the difference in propagation activity across the junction is due to differences in the number of cells for signal conduction or electrical connections between the cells. This study will advance our knowledge for understanding how the nerve, muscle and pacemaker cells work in concert in this junction, which is an important step for further clinical investigation of related disease.Read moreRead less
Understanding The Relationship Of Incretin Hormones, Gastric Emptying And Reactive Hypoglycaemia
Funder
National Health and Medical Research Council
Funding Amount
$132,743.00
Summary
Low blood glucose levels following a meal occur frequently in otherwise healthy people and those who have had surgery for weight loss. It affects quality of life adversely and current management is unsatisfactory. The proposed studies will use sophisticated techniques to evaluate the roles of the rate of stomach emptying and the so-called 'incretin' hormones which stimulate the release of insulin after a meal. The outcomes will have major implications for more rational management.
Establishment Of A Biomarker To Test Molecular Risk Of Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$834,448.00
Summary
Less than 20% of patients live 5 years after a diagnosis of gastric cancer (GC). This is due to the advanced stage at the time of diagnosis. We have no markers to monitor therapy of cancer. This proposal aims to use next generation sequencing to find specific genetic changes in a persons tumour that can be used to monitor therapy. We aim to use the same technology to group patients into high-risk or low risk for development of GC. This will allow specific screening only for those at high-risk.
Structural Basis For Helicobacter Pylori Adhesion To Host Epithelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$665,328.00
Summary
The aim of this grant is to understand how the bacteria that cause gastric cancer and ulcers interact with the cells that line the stomach. This information will be used to develop new treatments to combat disease.
Acid Resistance Mechanisms Of Helicobacter Pylori And Their Impact On Gastric Colonisation
Funder
National Health and Medical Research Council
Funding Amount
$287,036.00
Summary
The gastric bacterium, Helicobacter pylori, infects more than half the population of the globe. H. pylori may cause either no symptomatic disease, induce peptic ulcers or be responsible for one of the major killing cancers, gastric cancer. Millions die or suffer from this infection each year. Yet we are remarkably ignorant of why the infection causes these different patterns of disease. This project aims to provide evidence to show that the very mechanism the bacterium has acquired to help it re ....The gastric bacterium, Helicobacter pylori, infects more than half the population of the globe. H. pylori may cause either no symptomatic disease, induce peptic ulcers or be responsible for one of the major killing cancers, gastric cancer. Millions die or suffer from this infection each year. Yet we are remarkably ignorant of why the infection causes these different patterns of disease. This project aims to provide evidence to show that the very mechanism the bacterium has acquired to help it resist stomach acid and so live in the stomach, is responsible for these differences. I.e. The organism lives in different parts of the stomach due to differences in local acid at that site. If the acid in a particular part of the stomach is too high, the acid resistance mechanism cannot cope. If the acid is too low, the organism also cannot grow well. Because the bacterium has evolved to only thrive in a relatively narrow range of acid, it will behave very differently in these different parts of the stomach. This results in different diseases. Various populations in different countries of the world have different levels of acid production and this also explains why in some countries duodenal ulcers predominate and in others gastric ulcer- gastric cancer is the norm. Showing why H. pylori lives where it lives will provide fundamental information relevant to understanding some of the world s major diseases and will also provides insights relevant to the design of new therapeutic approaches.Read moreRead less
Improving Efficacy Of Vaccination Against The Gut Pathogen Helicobacter Pylori
Funder
National Health and Medical Research Council
Funding Amount
$504,000.00
Summary
Helicobacter pylori are bacteria which live in the stomachs of half the World's population, where they are the main cause of two types of stomach cancers, as well as stomach and duodenal ulcers. The development of a vaccine against this organism would have a major impact on these diseases. Unfortunately, while there has been some success in animal models, the results from clinical trials have so far been disappointing. A key issue with vaccines against H. pylori is their poor efficacy, i.e. alth ....Helicobacter pylori are bacteria which live in the stomachs of half the World's population, where they are the main cause of two types of stomach cancers, as well as stomach and duodenal ulcers. The development of a vaccine against this organism would have a major impact on these diseases. Unfortunately, while there has been some success in animal models, the results from clinical trials have so far been disappointing. A key issue with vaccines against H. pylori is their poor efficacy, i.e. although they produce a significant reduction in bacteria numbers in animal models, they do not clear all of the bacteria. The remaining bacteria are sufficient to continue to cause disease. It is currently not understood how these vaccines work in mice, which makes it very difficult to improve their design. An additional problem common to all human vaccines, is the lack of a suitable adjuvant. An adjuvant is a non-specific vaccine component which is required to activate the immune system. Thus, for an effective vaccine it is essential to identify suitable adjuvants which will work against H. pylori and can be used in people. The chief investigator on this project has been working in the H. pylori vaccine field, in both academia and industry, for 8 years. He very recently identified an immunisation regime which greatly increases the effectiveness of vaccination against H. pylori in an animal model. The main aim of this project is to further develop this novel discovery to identify key immune factors that are critical to making an improved vaccine. In addition, the two associate investigators are experts in the area of adjuvants for human vaccines, and will help to test new vaccine systems in the H. pylori model. If successful, this project will generate highly significant data that will strongly contribute towards the design of an improved vaccine strategy against H. pylori in people.Read moreRead less
The Role Of Capsulin, A New BasicHelix-Loop-Helix Factor, In Differentiation And Repair Of The Gastric Mucosa.
Funder
National Health and Medical Research Council
Funding Amount
$131,812.00
Summary
We aim to understand the role that a new factor plays in the processes whereby the lining of the stomach is continually renewed, and also repaired after injury due to inflammation and ulceration. Once we understand the role of this factor and how it works, we may be able to use this factor as a therapeutic to prevent the initial formation of inflammation and ulceration in the stomach that can lead to more serious diseases, such as cancer.
Helicobacter Pylori VacA Toxin: Modulation Of Human Mitochondrial Function By A Bacterial Pathogen
Funder
National Health and Medical Research Council
Funding Amount
$508,003.00
Summary
This work will greatly further our understanding of how a bacterium, Helicobacter pylori, causes stomach ulcers and cancer. We will use cutting edge model systems to study the VacA toxin that is secreted from the bacteria and is targeted to human cells. We will examine where the toxin goes and how it affects our cells. It is expected that the improved understanding that will arise from this work will assist researchers to better devise drugs against this prevalent pathogen.